Genetic Variant NM_016848.6:c.545+2084C>A (chr9-89110472-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016848.6(SHC3):c.545+2084C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 977,192 control chromosomes in the GnomAD database, including 21,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3935 hom., cov: 32)

Exomes 𝑓: 0.20 ( 17413 hom. )

Consequence

SHC3
NM_016848.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.881

Publications

6 publications found

Variant links:

Genes affected

SHC3 (HGNC:18181): (SHC adaptor protein 3) Enables phosphotyrosine residue binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within glutamatergic synaptic transmission and learning or memory. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SHC3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016848.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC3	NM_016848.6	MANE Select	c.545+2084C>A		intron	N/A	NP_058544.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC3	ENST00000375835.9	TSL:1 MANE Select	c.545+2084C>A		intron	N/A	ENSP00000364995.4	Q92529-1

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33582

AN:

151924

Hom.:

3915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.00848

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.202

AC:

166792

AN:

825150

Hom.:

17413

Cov.:

AF XY:

0.201

AC XY:

76740

AN XY:

381222

show subpopulations

African (AFR)

AF:

0.282

AC:

4419

AN:

15676

American (AMR)

AF:

0.242

AC:

236

AN:

974

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

951

AN:

5098

East Asian (EAS)

AF:

0.00882

AC:

AN:

3630

South Asian (SAS)

AF:

0.157

AC:

2559

AN:

16338

European-Finnish (FIN)

AF:

0.210

AC:

AN:

272

Middle Eastern (MID)

AF:

0.221

AC:

354

AN:

1604

European-Non Finnish (NFE)

AF:

0.203

AC:

152985

AN:

754500

Other (OTH)

AF:

0.192

AC:

5199

AN:

27058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

6130

12260

18391

24521

30651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7318

14636

21954

29272

36590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.221

AC:

33650

AN:

152042

Hom.:

3935

Cov.:

AF XY:

0.218

AC XY:

16203

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.283

AC:

11736

AN:

41480

American (AMR)

AF:

0.222

AC:

3398

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

696

AN:

3468

East Asian (EAS)

AF:

0.00850

AC:

AN:

5176

South Asian (SAS)

AF:

0.147

AC:

706

AN:

4812

European-Finnish (FIN)

AF:

0.201

AC:

2124

AN:

10570

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14311

AN:

67950

Other (OTH)

AF:

0.205

AC:

431

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1345

2690

4035

5380

6725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

356

712

1068

1424

1780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.219

Hom.:

1368

Bravo

AF:

0.226

Asia WGS

AF:

0.106

AC:

369

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.41

(source)

DANN

Benign

0.38

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over